The Alternative: EDHF

doi:10.1006/jmcc.1998.0840

Journal of Molecular and Cellular Cardiology

Volume 31, Issue 1, January 1999, Pages 15-22

https://doi.org/10.1006/jmcc.1998.0840 Get rights and content

Abstract

Endothelium-dependent relaxations cannot be fully explained by the release of either NO or/and prostacyclin. Another unidentified substance(s) which hyperpolarizes the underlying vascular smooth muscle cells may contribute to endothelium-dependent relaxations, especially in small arteries. It has been termed endothelium-derived hyperpolarizing factor (EDHF). In blood vessels from various species including humans, endothelium-dependent relaxations are partially or totally resistant to inhibitors of NO synthase and cyclooxygenase and are observed without an increase in the intracellular level of cyclic nucleotides in the vascular smooth muscle cells. In some species (canine, porcine and human) nitrovasodilators do not cause hyperpolarization while in other (rat, guinea-pig, rabbit), they evoke glibenclamide-sensitive hyperpolarization, suggesting the involvement of ATP-dependent potassium channels. In contrast, hyperpolarizations caused by EDHF are insensitive to glibenclamide but are inhibited by apamin or the combination of charybdotoxin plus apamin, indicating that NO and EDHF interact with two different targets. The existence of EDHF as a diffusable substance has been demonstrated under bioassay conditions whereby the source of EDHF was either native vascular segments or cultured endothelial cells. The identification of EDHF may allow a better understanding of its physiological and pathophysiological role(s).

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Empagliflozin at concentrations >1000 μM did not induce further vasodilation, so 1000 μM was the maximum concentration used to evoke vasodilation. The vascular endothelium plays an important role in regulating vascular tone by releasing the endothelium-derived relaxing factors (EDRFs) nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin (Feletou and Vanhoutte, 1999). To explore whether the endothelium influences the vasodilatory effects of empagliflozin, we analyzed the effects of empagliflozin on endothelium-denuded aortic rings.
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Endothelial Dysfunction: a Novel Therapeutic TargetThe Alternative: EDHF

Abstract

Endothelial Dysfunction: a Novel Therapeutic Target
The Alternative: EDHF